There is currently an enormous interest in the role of immunologic events during human reproduction. Medical research teams are actively investigating the immunologic processes that exist in normal fertile and subfertile circumstances.
There appears to be considerable pressure (from both the infertile community and the research community) to make available “experimental” immunologic treatments to couples desperate to improve their chances for successful reproduction. Generally, the risks and benefits of any treatment offered should be discussed in as much detail as possible. When offering an experimental treatment this should also be disclosed to the couple being treated.
At this time (2002), there is no clear “standard of care” with regard to recommended immunologic diagnostic tests or treatment options. There are few prospective controlled clinical trials in the literature to guide our medical decisions in this area. Therefore, when testing and/or treatment are offered (for immunologic barriers to fertility) a frank discussion of the (currently) experimental nature of these procedures should be included. I often refer these couples to a University program where they can enter into a (research) treatment protocol so that their clinical information can be (additionally) used to promote an improved understanding of these issues.
Antiphospholipid antibodies comprise a commonly recognized antibody system known to impact fertility (especially pregnancy loss). When the elevated antiphospholipid antibodies (including anticardiolipin antibody levels) are associated with recurrent pregnancy loss, a thrombotic event (such as placental blood clots) and/or thrombocytopenia then this is referred to as the antiphospholipid syndrome.
Antiphospholipid antibodies (APA) may also be associated with success (pregnancy rates) at IVF. It is recognized that infertile patients appear to have an increased rate of positive APA compared to fertile controls. However, several studies in the literature suggest that there is no significant association between APA and IVF pregnancy rates. One study suggests improved fertility rates when women testing positive for APA are treated with mini-aspirin and heparin (compared to women testing positive for APA without treatment), but significant methodologic concerns with this study limit acceptance of this finding. At this time (2002) it is certainly not clear that the increased prevalence of positive APA in the infertility population has any direct bearing on their pregnancy rates. It will be important to follow the results of larger multicenter trials concerning this possible association.
Reproductive immunophenotype analysis has become popular in research groups that are focused on the immunologic basis of infertility. This analysis determines the distribution of peripheral lymphocyte populations, each population having different biologic functions. The natural killer cells (including lymphocytes expressing the cell surface marker “cluster differentiation (CD) 56”) are less specific than other lymphocytes in determining which foreign material is attacked and are the predominant white blood cell population recruited into the secretory endometrium during the window of implantation. Therefore, CD 56 cells may be more involved in placental site rejection (immunologic attack) than other lymphocytes.
One clinical trial involving over 1000 IVF patients at a leading IVF center in the USA correlated IVF success with immunophenotype analysis and found no significant relationship (including IVF success and natural killer cell activity). Therefore, the immunophenotype analysis has questionable clinical application in the context of ARTs.
It appears that some immunologically based treatments may (favorably) affect fertility within certain subsets of the general infertile population. Treatments that are occasionally used include heparin, glucocorticoids (prednisone), and IV Ig. Unfortunately, at this time it is not possible to reliably determine which couples benefit from these potentially hazardous and often expensive treatments. It is also unclear why these treatments sometimes seem to be helpful. It will be very important to follow this line of research since it is likely that clinically useful diagnostic tests and treatment options will (eventually) become available.